During the period following development or infliction of serious physical damage to the skin, by way of for example, severe burns, wounds, pressure ulcers, and the like, the injured area is extremely unstable physiologically. Following such injury or trauma, the normal physiological processes of the area in question may be severely compromised. Disruption in the normal pattern of skin growth, blood flow, and immunity may all be impaired to some extent by the trauma to the region. The health care provider treating such damaged tissue must therefore be able to control and eventually reverse these undesirable effects, while at the same time stimulating the processes that are necessary to achieve healing of the area.
Because of the variety of different systems which may be adversely affected by such injury, it is difficult to find a single agent which will be effective in controlling the various sources of the problems. For example, one of the most severe difficulties encountered is the immediate colonization of the wound by a variety of different types of microbial species. Common invaders of a wound site are known pathogens such as Staphylococcus aureus, as well as a number of opportunistic pathogens, such as Escherichia coli or Pseudomonas aeruginosa. Various yeasts, particularly Candida albicans, may also be found at the wound. Although a number of antimicrobial agents for topical application are known, none has proven to be without some serious disadvantage. For example, silver sulfadiazine, the current antibacterial agent of choice, is effective against gram-positive and gram-negative bacteria but many resistant strains have developed in the course of its use, particularly in the genus, Pseudomonas. Similarly, the commonly used 10% pvp iodine, although effective against both gram-positive and gram-negative bacteria, can be quite painful to the patient upon application, kills white cells in the wound, specifically polymorphonuclear cells, lymphocytes, monocytes, macrophages, fibroblasts, endothelial cells and keratinocytes and may cause sensitization of an area already severely traumatized. Other known antibacterial agents may be hampered in their use by low diffusibility of the composition, or a range of activity that covers relatively few types of microbes. Expense, as with substances such as the various silver salts, is also a factor to be considered.
Related to the invasion by microbes of the wound site is the generally decreased circulation which is also observed in many cases. For example, in decubitus or stasis ulcers, a cessation of blood flow may develop gradually, whereas an acute cessation of flow may occur in thermo-radiation and chemical burns. In either case the decrease in the rate of blood flow means a corresponding decrease in the provision to the cells of nutrients and oxygen. Thus deprivation in turn leads to necrosis of tissue in the poorly supplied region, which will be followed by the invasion of the unwanted bacteria and fungi. In order for healing to proceed, the damaged area must not only be rid of any lingering microbial infection, but also must have a restored blood flow, which will provide sufficient nutrient and oxygen supply to support regeneration of the wounded region. In the ideal situation, the increased blood flow should also be accompanied by the formation of healthy granulation tissue. The latter is a layer of highly vascularized tissue, containing numerous fibroblasts and collagen and ground substance, which supports the normal wound healing processes of recollagenation and re-epithelialization.
Another very critical aspect of the wound healing process is the initiation of wound closure. This is generally a two-stage process, comprising contraction and epidermal migration. Contraction is the process of bulk skin movement from the edges of the wound, while migration is the separation and movement of activated epidermal cells over the surface of the wound. Because contraction itself may lead to some scarring, it is preferable to be able to speed healing in a manner which will increase the process of epidermal migration. The process of migration is characterized by a stimulation of mitosis in the epidermal cells, accompanied by movement across the wound site. The extent to which epidermal migration, and thus wound closure, can be promoted will also in some cases determine whether or not additional skin grafting is required to complete the healing of the wound.
It is thus evident that a large number of different factors must be controlled and/or stimulated in order to achieve thorough regeneration of the damaged tissue. Since the processes involved, and the mechanisms controlling them, are so diverse, it has proven difficult to pinpoint a single treatment composition or method which is capable of aiding and promoting most or all of the required processes simultaneously. As noted above with respect to the various antibacterial agents available, the majority of wound healing compositions and delivery systems presently available suffer from one or another deficiencies, whether it be in complexity of application, insufficient ability to control precise application of the dressing, irritation caused to the patient, or expense. For example, with powder compositions, contact with the wound is limited to where the powder falls on the wound and even with careful application, more powder than necessary can be used and it is difficult to apply the powder to all areas of the wound. Use of a gel medium of selected viscosity is more effective at accelerating mitotic division of the epidermal cells, fibroblasts, and endothelial cells of the connective tissue because the gel, having fluid properties, flows into all areas of the wound and therefore increases delivery of wound-healing agents to the wound more directly.